Beruflich Dokumente
Kultur Dokumente
Beriplast P Combi-Set
Qualitative composition
Combi-Set I:
Active substances
Human fibrinogen, Coagulation Factor XIII (human), Aprotinin (bovine)
Combi-Set II:
Active substances
Human thrombin, Calcium Chloride
Quantitative composition
Combi-Set I per 1 ml
Vial 1 Fibrinogen Concentrate:
total dried substance 174 mg
fibrinogen (human plasma protein fraction) 90 mg
coagulation factor XIII (human plasma protein fraction) 60 IU
Vial 2 Aprotinin Solution:
volume 1.0 ml
bovine lung aprotinin 1000 KIU*
corresponding to 0.56 PEU**
* KIU = Kallikrein Inactivator Unit
** PEU = Ph. Eur. Unit (1 PEU ^ 1800 KIU)
Combi-Set II per 1 ml
Vial 3 Thrombin:
total dried substance 7.6 mg
with a human plasma protein fraction thrombin activity 500 IU
Vial 4 Calcium Chloride Solution:
volume 1.0 ml
calcium chloride dihydrate 5.9 mg
3. PHARMACEUTICAL FORM
4. CLINICAL PARTICULARS
Posology
The volume of Beriplast to be applied and the frequency of application should always be
oriented towards the underlying clinical needs of the patient.
The dose to be applied is governed by variables including, but not limited to, the type of
surgical intervention, the size of the area and the mode of intended application, and the
number of applications.
Application of the product must be individualised by the treating physician. In clinical trials,
the individual dosages have typically ranged from 0.5 to 4 ml. For some procedures (e.g.,
liver traumata, or the sealing of large burned surfaces) larger volumes (10 ml or more) may
be required.
The initial volume of the product to be applied at a chosen anatomic site or target surface
area should be sufficient to entirely cover the intended application area. The application can
be repeated, if necessary.
Paediatric population
The safety and efficacy of Beriplast in children and adolescents has not yet been established
in controlled clinical studies.
CSL Behring
Beriplast P Combi-Set
Method of administration
For epilesional use.
For instructions on reconstitution of the medicinal product before administration, see section
6.6.
The reconstituted solutions (of vial 1 and 3) are to be administered locally to the tissue
(sequentially or in combination). Unlike other haemostatic agents that must be removed
once haemostasis is achieved, Beriplast remains in place after application and is degraded
by the normal physiological process of clot lysis.
Prior to applying Beriplast the surface area of the wound needs to be dried by standard
techniques (e.g. intermittent application of compresses, swabs, use of suction devices).
Beriplast should only be reconstituted and administered according to the instructions and
with the devices as provided with this product. See section 6.6 for more detailed
instructions.
4.3 Contraindications
Before administration of Beriplast care is to be taken that parts of the body outside the
desired application area are sufficiently protected (covered) to prevent tissue adhesion at
undesired sites.
As with any protein product, allergic type hypersensitivity reactions are possible. Signs of
hypersensitivity reactions include hives, generalised urticaria, tightness of the chest,
wheezing, hypotension, and anaphylaxis. If these symptoms occur, the administration has to
be discontinued immediately.
Beriplast contains bovine protein (aprotinin). Even in case of strict local application, there is
a risk of anaphylactic reactions, linked to the presence of bovine aprotinin. The risk seems
higher in case of previous exposure, even if it was well tolerated. Therefore any use of
aprotinin or aprotinin-containing products should be documented in the patients’ records.
Virus safety
Standard measures to prevent infections resulting from the use of medicinal products
prepared from human blood or plasma include selection of donors, screening of individual
donations and plasma pools for specific markers of infections and the inclusion of effective
manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal
products prepared from human blood or plasma are administered, the possibility of
transmitting infective agents cannot be totally excluded. This also applies to unknown or
emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as human
immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). The
measures taken may be of limited value against non-enveloped viruses such as hepatitis A
virus and parvovirus B19.
Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for
individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).
It is strongly recommended that every time that Beriplast is administered to a patient, the
name and batch number of the product are recorded in order to maintain a link between the
patient and the batch of the product.
4.5 Interaction with other medicinal products and other forms of interaction
Fertility
No fertility data are available.
Not relevant.
Gastrointestinal disorders
Administration in the endoscopic treatment of gastrointestinal bleeding can cause tissue
damage, which can lead to formation of intramural haematoma (see section 4.4).
Vascular disorders
Inadvertent intravascular injection could lead to thromboembolic event and DIC, and there
is also a risk of anaphylactic reaction (see section 4.4).
For safety information with respect to transmissible agents see section 4.4.
4.9 Overdose
5. PHARMACOLOGICAL PROPERTIES
The fibrin adhesion system initiates the last phase of physiological blood coagulation.
Conversion of fibrinogen into fibrin occurs by the splitting of fibrinogen into fibrin
monomers and fibrinopeptides. The fibrin monomers aggregate and form a fibrin clot.
Factor XIIIa, which is activated from factor XIII by thrombin, crosslinks fibrin. Calcium
ions are required for both, the conversion of fibrinogen and the crosslinkage of fibrin.
As wound healing progresses, increased fibrinolytic activity is induced by plasmin and
decomposition of fibrin to fibrin degradation products is initiated.
Single dose toxicity data reveal no special hazard for humans, beyond the information
included in other parts of the SPC. Due to its nature as well as its special method of
application no genotoxicity and cancerogenicity studies have been performed.
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Beriplast P Combi-Set
6. PHARMACEUTICAL PARTICULARS
Combi-Set I
Vial 1: powder
human albumin, L-arginine hydrochloride, L-isoleucine, sodium chloride, sodium
citrate dihydrate, sodium L-glutamate monohydrate
Vial 2: solvent
sodium chloride, water for injections
Combi-Set II
Vial 3: powder
sodium chloride, sodium citrate-dihydrate
Vial 4: solvent
water for injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those
mentioned in section 6.6.
2 years
Chemical and physical in-use stability has been demonstrated for 24 hours at room
temperature (up to max. +25 °C). However, from a microbiological point of view, unless the
method of reconstitution precludes the risk of microbial contamination, the product should
be used immediately.
Store in a refrigerator (2 °C - 8 °C). Do not freeze. Keep the container in the outer carton in
order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
CSL Behring
Beriplast P Combi-Set
Immediate containers
Injection vials:
Colourless glass,
- Type I acc. to Ph. Eur. in case of Fibrinogen Concentrate 0.5 and 1 ml, Aprotinin
Solution, Thrombin and Calcium Chloride Solution
- Type II acc. to Ph. Eur. in case of Fibrinogen Concentrate 3 ml each sealed with rubber
stopper and aluminium cap.
Presentations
Pack for Beriplast P 0.5 ml
Combi-Set I for preparing the fibrinogen solution, consisting of vials 1 and 2 linked together
via a transfer device:
Vial 1 containing powder of fibrinogen and coagulation factor XIII
Vial 2 containing aprotinin solution
Combi-Set II for preparing the thrombin solution, consisting of vials 3 and 4 linked together
via a transfer device:
Vial 3 containing thrombin powder
Vial 4 containing calcium chloride solution
Application set, consisting of:
2 sterile disposable tuberculin syringes
Pantaject application kit
2 sterile disposable spray-tips
4 sterile disposable cannulas
Beriplast must not be used after the expiry date given on the pack and container.
The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or
have deposits. Reconstituted solutions should be inspected visually for particulate matter
and discoloration prior to administration.
– Incline Vial 1 (fibrinogen solution/blue marking) and draw up the contents into the blue
marked syringe. Completely draw up the contents of Vial 3 (thrombin solution/red
marking) into the red marked syringe (see Fig. 4).
Use the reconstituted solutions immediately after withdrawal into the syringes.
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements.
Application
Prior to applying Beriplast the surface area of the wound needs to be dried by standard
techniques (e.g. intermittent application of compresses, swabs, use of suction devices).
Handling of the application kit for Beriplast (see diagram on the application kit):
Remove the needles from the syringes filled with the fibrinogen solution (blue marking) and
thrombin solution (red marking).
(A) Insert the Y-piece (3) in the conical recess of the syringe holder (4).
(B) Firmly connect to the Y-piece (3) the syringes filled with the fibrinogen solution
(1/blue marking) and thrombin solution (2/red marking).
(C) Snap both syringes into the syringe holder (4).
(D) Connect the grip plate (5) to the syringe plungers to prevent jamming of the syringe
plungers and to ensure smooth forward movement.
(E) Finally firmly screw on the spray tip (6) or the application cannula (7) (both equipped
with a Luer-Lock connector).
For covering large wound surfaces the fibrin sealant can be sprayed using the enclosed
spray-tips, or used in combination with fleece consisting of e.g. polyglycolic acid or
collagen.
Before use in the wound region the system must be checked for blockages. Never push the
syringe plungers against a resistance! Any interruption in the application, even of short
duration, results in blockage of both either the spray tip or application cannula. In such cases
the spray tip or application cannula is unsuitable for further use and must be replaced. For
this purpose the 0.5 and 1 ml Beriplast packages contain two spray tips and the 3 ml
packages contain three spray tips; each package contains four blunt application cannulas.
By applying an even pressure to the grip plate – like for an injection – the fibrin sealant is
sprayed from the spray tip as a fine, even aerosol. The best distance is about 10 cm. A fine
film of fibrin sealant forms on the tissue to be coated.
CSL Behring
Beriplast P Combi-Set
April 2013